title: Genome-Wide Gene Expression Profiling Revealed a Critical Role for GATA3 in the Maintenance of the Th2 Cell Identity.
abstract: Functionally polarized CD4+ T helper (Th) cells such as Th1, Th2 and Th17 cells are central to the regulation of acquired immunity. However, the molecular mechanisms governing the maintenance of the polarized functions of Th cells remain unclear. GATA3, a master regulator of Th2 cell differentiation, initiates the expressions of Th2 cytokine genes and other Th2-specific genes. GATA3 also plays important roles in maintaining Th2 cell function and in continuous chromatin remodeling of Th2 cytokine gene loci. However, it is unclear whether continuous expression of GATA3 is required to maintain the expression of various other Th2-specific genes. In this report, genome-wide DNA gene expression profiling revealed that GATA3 expression is critical for the expression of a certain set of Th2-specific genes. We demonstrated that GATA3 dependency is reduced for some Th2-specific genes in fully developed Th2 cells compared to that observed in effector Th2 cells, whereas it is unchanged for other genes. Moreover, effects of a loss of GATA3 expression in Th2 cells on the expression of cytokine and cytokine receptor genes were examined in detail. A critical role of GATA3 in the regulation of Th2-specific gene expression is confirmed in in vivo generated antigen-specific memory Th2 cells. Therefore, GATA3 is required for the continuous expression of the majority of Th2-specific genes involved in maintaining the Th2 cell identity.
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, Chiba City, Japan ; Pharmaceutical Research Laboratory, Research Division, Nihon Pharmaceutical Co Ltd, Narita City, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sasaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Onodera
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hosokawa
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Shu
authors.initials: S
authors.lastname: Horiuchi
authors.forename: Junji
authors.initials: J
authors.lastname: Yamashita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering / Q000235:genetics; D018121:Receptors, Cytokine / Q000235:genetics; D018418:Th2 Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D034741:RNA, Small Interfering; D018121:Receptors, Cytokine